Abstract | BACKGROUND:
Glucagon-like peptide 2 (GLP-2) is a recently identified intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. We hypothesized that GLP-2 administration would be beneficial in chemotherapy-induced enteritis either by preventing injury or by promoting recovery. MATERIAL AND METHODS: Rats received no drug (control), chemotherapy alone [ 5-fluorouracil (5-FU), 190 mg/kg, ip] (Chemo), 5-FU followed by 3 days of GLP-2 analog (ALX-0600, 0.1 microg, sc twice daily) (CH-G), or GLP-2 analog for 6 days prior to 5-FU and for 3 days afterward (G-CH-G). Animals were pair fed. Rats received 5-bromo-2-deoxyuridine (Br-dU, 50 mg/kg, 2.5 h prior to sacrifice on Day 3 postchemotherapy) for immunohistochemical assessment of cellular proliferation. RESULTS:
Chemotherapy induced significant reductions in body weight, villus height, and crypt depth compared with controls. Intestinal wet weight, villus height, and crypt depth were significantly higher for the CH-G group compared with the Chemo group. The CH-G group also showed a significant improvement in villus height compared with the G-CH-G group. Crypt depth, but not jejunal wet weight or villus height, was significantly improved in the G-CH-G group compared with the Chemo group. The percentage of Br-dU-labeled cells in the intestinal crypts did not differ among the groups. CONCLUSIONS: These results suggest, for the first time, that GLP-2 treatment initiated after chemotherapy administration enhances intestinal recovery. In contrast, GLP-2 treatment initiated prior to chemotherapy administration to prevent injury has less beneficial effect. GLP-2 administration may be beneficial to patients suffering from chemotherapy-induced enteritis.
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Authors | A Tavakkolizadeh, R Shen, P Abraham, N Kormi, P Seifert, E R Edelman, D O Jacobs, M J Zinner, S W Ashley, E E Whang |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 91
Issue 1
Pg. 77-82
(Jun 01 2000)
ISSN: 0022-4804 [Print] United States |
PMID | 10816354
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright 2000 Academic Press. |
Chemical References |
- Antimetabolites, Antineoplastic
- Glucagon-Like Peptide 2
- Peptides
- Glucagon-Like Peptides
- Bromodeoxyuridine
- Fluorouracil
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(adverse effects)
- Body Weight
- Bromodeoxyuridine
(analysis)
- Enteritis
(chemically induced, drug therapy)
- Fluorouracil
(adverse effects)
- Glucagon-Like Peptide 2
- Glucagon-Like Peptides
- Intestinal Mucosa
(chemistry, cytology, drug effects)
- Jejunum
(chemistry, cytology, drug effects)
- Male
- Morbidity
- Peptides
(pharmacology)
- Rats
- Rats, Sprague-Dawley
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